Boron trifluoride etherate → Tert-butyl 5,5,5-trifluoropentanoate

HRID 921256Notes

Reaction equation

HRID 921256 reaction equation
[F:1][C:2]([F:10])([F:9])[CH2:3][CH2:4][CH2:5][C:6]([OH:8])=[O:7].ClC(Cl)(Cl)C(=N)O[C:15]([CH3:18])([CH3:17])[CH3:16].B(F)(F)F.CCOCC.C([O-])(O)=O.[Na+]>C1COCC1.CCCCCC>[F:1][C:2]([F:10])([F:9])[CH2:3][CH2:4][CH2:5][C:6]([O:8][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:7]

Participants

7

Reactant 4

HCID 8000Boron trifluoride etherateHCID 516892Sodium BicarbonateHCID 2734700Tert-butyl 2,2,2-trichloroethanimidateHCID 27824465,5,5-trifluoropentanoic Acid

Product 1

HCID 86671369Tert-butyl 5,5,5-trifluoropentanoateYield 98%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of 5,5,5-trifluoropentanoic acid (5 g, 32.0 mmol) in THF (30 mL) and hexane (30 mL) at 0° C., was added tert-butyl 2,2,2-trichloroacetimidate (11.46 mL, 64.1 mmol). The mixture was stirred for 15 min at 0° C. Boron trifluoride etherate (0.406 mL, 3.20 mmol) was added and the reaction mixture was allowed to warm to room temperature overnight. To the clear reaction mixture was added solid NaHCO3 (5 g) and stirred for 30 min. The mixture was filtered through MgSO4 and washed with hexanes (200 mL). The solution was allowed to rest for 45 min, and the resulting solid material was removed by filtering on the same MgSO4 filter again, washed with hexanes (100 mL) and concentrated under reduced pressure without heat. The volume was reduced to about 30 mL, filtered through a clean fritted funnel, washed with hexane (5 mL), and then concentrated under reduced pressure without heat. The resulting neat oil was filtered through a 0.45 μm nylon membrane filter disk to provide Intermediate S-1G (6.6 g, 31.4 mmol 98% yield) as a colorless oil: 1H NMR (400 MHz, CDCl3) δ ppm 1.38 (s, 9H) 1.74-1.83 (m, 2H) 2.00-2.13 (m, 2H) 2.24 (t, J=7.28 Hz, 2H).

Workup

  1. temperatureto warm to room temperature overnight
  2. stirringstirred for 30 min
  3. filtrationThe mixture was filtered through MgSO4
  4. washwashed with hexanes (200 mL)
  5. waitto rest for 45 min
  6. customthe resulting solid material was removed
  7. filtrationby filtering on the same MgSO4
  8. filtrationfilter again
  9. washwashed with hexanes (100 mL)
  10. concentrationconcentrated under reduced pressure
  11. temperaturewithout heat
  12. filtrationfiltered through a clean fritted funnel
  13. washwashed with hexane (5 mL)
  14. concentrationconcentrated under reduced pressure
  15. temperaturewithout heat
  16. filtrationThe resulting neat oil was filtered through a 0.45 μm nylon membrane
  17. filtrationfilter disk
  18. customto provide Intermediate S-1G (6.6 g, 31.4 mmol 98% yield) as a colorless oil

Sources & evidence

ORD record
ord-06bc43413273408a83738bab5b966533
Source dataset
uspto-grants-2016_03
Patent number
US09273014B2

Reaction notes

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